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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology of dystonia remains unclear in comparison with other movement disorders. Recent data suggest that there may exist in dystonia an increased thalamic drive to the mesial premotor cortex. To test this hypothesis, we induced overactivity of the motor thalamus by injecting a GABA-A (gamma-aminobutyric acid) antagonist (bicuculline) into the rostral (pallidal) and caudal (cerebellar) ventrolateral nuclei of the thalamus in both hemispheres of one monkey. Dystonic postures were observed in the contralateral limbs and axis. Electromyographic recordings revealed bursts of muscular activation with co-contractions during spontaneous dystonic movements and alterations in muscular patterns during sequential visually guided arm movements. The type of dystonia depended on the site of injections. Rostral thalamic injections induced more severe dystonic postures, whereas myoclonic jerks predominated following caudal injections. We conclude that these two distinct clinical patterns, which are frequently associated in humans, are probably due to a dysfunctioning of segregated thalamic projections to the supplementary motor area (from the rostral part) and to the primary motor cortex (from the caudal part).
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PMID:Bicuculline injections into the rostral and caudal motor thalamus of the monkey induce different types of dystonia. 1076 34

Cannabis may have medicinal uses in a variety of diseases. The neural mechanisms underlying dystonia involve abnormalities within the basal ganglia-in particular, overactivity of the lateral globus pallidus (GPl). Cannabinoid receptors are located presynaptically on GABA terminals within the GPi, where their activation reduces GABA reuptake. Cannabinoid receptor stimulation may thus reduce overactivity of the GPl and thereby reduce dystonia. A double-blind, randomised, placebo-controlled, crossover study using the synthetic cannabinoid receptor agonist nabilone in patients with generalised and segmental primary dystonia showed no significant reduction in dystonia following treatment with nabilone.
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PMID:Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. 1183 52

Functional neuroimaging using positron emission tomography (PET), and more recently functional MRI (fMRI) and magnetoencephalography (MEG), is a valuable tool to study functional anomalies in dystonia. Activation studies have contributed to a better understanding of cerebral dysfunction in dystonia showing two main types of abnormalities: changes in activation levels during performance of sensory or motor tasks and disorganization of the selectivity of neuronal representations. In primary dystonia, most PET and fMRI studies have shown overactivity in premotor and prefrontal areas and underactivation of primary sensorimotor areas. In secondary dystonia, premotor and prefrontal areas are similarly overactive as well as primary sensorimotor areas. Altered selectivity of neuronal representations has been described more recently along cortico-subcortical circuits. The loss of neuronal selectivity may contribute to the loss of selectivity of muscular contractions observed in dystonia. Spectroscopic MRI may also be used to measure GABA levels, which are decreased in the cortex and basal ganglia in these patients.
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PMID:[Dystonia: contributions of functional imaging and magnetoencephalography]. 1461 75

It has previously been reported that men with developmental stuttering showed reduced concentration of copper in the blood, and a negative correlation between the copper level and the severity of stuttering. Disorders of copper metabolism may result in dysfunction of the basal ganglia system and dystonia, a motor disorder sharing some traits of stuttering. It has been shown that copper ions affect the dopamine and the GABA systems. With this background we investigated the plasma level of copper, the copper binding protein ceruloplasmin, and the estimated level of free copper in stuttering adults. Sixteen men with developmental stuttering were compared with 16 men without speech problems. The samples were assayed in one batch in a pseudorandom and counterbalanced order. No significant differences were found between stuttering men and the control group in any of the biological variables, and no negative correlation between copper and the general severity of stuttering was shown. On the contrary, an explorative analysis resulted in a positive correlation between high plasma copper and superfluous muscular activity during stuttering (r=0.51, p=0.04). This result indicates that there is no relation between developmental stuttering and low plasma copper in the main population of stuttering adults.
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PMID:Copper in developmental stuttering. 1603 97

Various types of hereditary dystonia are regarded as a basal ganglia disorder, but the underlying mechanisms are still unknown. In the dt hamster, a genetic animal model of age-dependent paroxysmal dystonia, recent studies demonstrated a reduced density of striatal parvalbumin-immunoreactive (PV) GABAergic interneurons at an age of maximum severity of dystonia in comparison with age-matched nondystonic controls. So far, alterations of other types of striatal interneurons in dt hamsters cannot be excluded. Therefore, we determined the density of calretinin-immunoreactive (CR) interneurons in the dt mutant at an age of maximum severity and after spontaneous remission of dystonia in comparison with age-matched nondystonic controls using an image analysis system and a stereologic counting method in a blinded fashion. At an age of maximum severity of dystonia, CR interneuron density was significantly lower in dt hamsters in comparison with controls (-20%), whereas no significant differences between the animal groups could be detected after spontaneous remission of dystonia. The comparison of CR interneuron density between young hamsters with those at an age of > 90 days revealed a significant ontogenetic decrease of CR interneurons in both animal groups (dt hamsters: -38%, controls: -54%). These results demonstrate that alterations of striatal interneuron density in dt mutants are not restricted to PV ones. A deficit of CR interneurons that coexpress GABA may contribute to previous findings of disinhibition of striatal projection neurons in the dt mutant at an age of maximum expression of dystonia.
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PMID:Age-dependent alterations of striatal calretinin interneuron density in a genetic animal model of primary paroxysmal dystonia. 1614 87

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.
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PMID:Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice. 1638 Jul 13

This article reviews three of the involuntary hyperkinetic motor disorders that affect the orofacial region, namely orofacial dystonia, oromandibular dyskinesia, as well as medication-induced extrapyramidal syndrome-dystonic reactions. Specifically, it discusses and contrasts the clinical features and management strategies for spontaneous primary and drug-induced motor disorders in the orofacial region. The article provides a list of medications reported to cause drug-related extrapyramidal motor activity above and beyond the more commonly known antipsychotics medications. It provides a needed update because the number and use of medications causing involuntary jaw muscle activity are increasing. For example, selective serotonin reuptake inhibitors (SSRI), stimulant medications and illegal drugs have all been reported to induce an orofacial motor activation as adverse reactions. This article also discusses briefly the genetic and traumatic events associated with spontaneous dystonia. Finally, this article presents an approach for management of the orofacial motor disorders that involves the following three steps: (1) collect a full clinical history and examination, including magnetic resonance imaging of the brain; (2) after ruling out CNS disease, adverse medications reactions and local pathology, try one or more of the motor-suppressive medications that may be helpful in these cases (e.g., cholinergic receptor antagonizers or blockers, and GABA-ergic including benzodiazepines); and (3) if the disorder is severe enough and focal enough to consider, and motor-suppressive medications are not adequate, then consider botulinum toxin injections. The contraindications, side effects, and usual approach for these medications and injections are discussed.
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PMID:Medical management of oral motor disorders: dystonia, dyskinesia and drug-induced dystonic extrapyramidal reactions. 1696 75

We report a 67-year-old woman with idiopathic oromandibular dystonia (OMD). She could neither open the mouth nor take meals due to involuntarily strong mouth-closing. The movement of face, pharynx and tongue were normal, and she could open the mouth slightly when jaw and cheek were touched (sensory trick). Chvostek sign and Trousseau sign were negative, and opisthotonus was not recognized. The laboratory data including calcium, phosphorous and cerebrospinal fluid were within normal limits, head and cervical MRI, temporomandibular joints-Xp and needle electromyography were normal. The surface electromyography revealed that masseter and chin muscles contracted synchronously. This result meant dystonia around the mouth. The clinical course and physical examination did not support the diagnosis of tetanus, tetany or bulldog response. She was diagnosed as OMD. She had peroral administration of baclofen, because this drug is a GABA-derivative and acts as a muscular relaxant. Her clinical symptoms and dystonic pattern on the surface electromyography improved markedly after the administration. Baclofen is an effective drug for treatment of oromandibular dystonia.
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PMID:[Case of oromandibular dystonia presenting with severe impairment of mouth-opening, and a marked effect by administration of baclofen]. 1726 Aug 12

Baclofen (beta-p-chlorophenyl-GABA) binds to a number of spinal and cerebral sites and depresses the excitability of motor neurons. Intrathecal administration induces much higher CSF concentrations compared to the limited passage through the blood-brain barrier after oral administration. The development of reliable implanted pumps allows long-term intrathecal baclofen treatment (ITB). Baclofen is mainly an antispastic drug and the main indication of ITB is generalized lower limb spasticity in spinal cord injury and multiple sclerosis. The side-effects are due to either drug over-dose or withdrawal and to malfunctions of the implanted device (disconnections of the catheter, infections, etc.). Large numbers of patients have been treated over the past twenty years. More recently, baclofen has been used in the treatment of spasticity of cerebral origin, and in the treatment of other motor disorders, mainly dystonia. The results in cerebral palsy are promising and ITB's role will probably grow in the management of the movement disorders of these children. Further studies are required on the exact site of action, on the possible association with other drugs, especially clonidine and on the development of sustained release formulations.
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PMID:Intrathecal baclofen in the treatment of spasticity, dystonia and vegetative disorders. 1769 79

Several lines of evidence suggest that GABA-ergic neurotransmission plays a role in the pathogenesis of primary dystonia in humans. In this study, we tested the hypothesis that mutations in the GABRA1, GABRB3, and GABRG2 genes encoding the alpha1, beta3, and gamma subunits of the GABA(A) receptor are involved in familial primary dystonia. All exons and exon-intron boundaries of the above genes were amplified by PCR from genomic DNA in 28 patients who had primary dystonia and a positive family history but had no mutation in any other genes known to be involved in primary dystonia. The PCR products were analyzed by single strand conformation polymorphism followed by sequencing of variant conformers compared with normal controls (n = 54). We found no mutations in these genes. We did, however, find a new polymorphism, 559 + 80G>A in intron 5 of GABRA1, and we also confirmed several that were previously reported, including 315C>T in exon 3 and 588C>T in exon 5 of GABRG2, but there were no significant differences between controls and patients in the allele and genotype frequencies of these polymorphisms. In conclusion, mutations of GABRA1, GABRB3, and GABRG2 appear not to play a major role in the development of familial primary dystonia.
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PMID:Screening of GABA(A)-receptor gene mutations in primary dystonia. 1788 May 75


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